Neural injury caused by physical trauma, ischemia, or disease can result in profound disability or death. Such disabilities, which may be physical and/or mental, include loss of movement, impaired sensory perception, loss of cognitive functions, seizures, and emotional and personality disorders. Given the prevalence and possible severity of these disabilities, neural injury takes a heavy toll on individuals and society. Accordingly, there is a need for treatments which facilitate the repair of damaged nerves and neuronal pathways. At present, there is no effective treatment for central nervous system (CNS) injuries.
Brain physical trauma, spinal cord compression or transection, ischemia, or surgery cause hypoxia which initiates a cascade of molecular events leading to neural injury. After nerve damage has occurred, a patient's prognosis depends on the ability of damaged nerves to repair so that neuronal connectivity can be restored. Therefore, the potential benefit of a treatment which facilitates neural repair and the re-establishment of neuronal connectivity would be tremendous.
Neurons in the peripheral nervous system can regenerate and re-innervate their targets. However, scar tissue that forms as a result of the injury can obstruct the growth of regenerating peripheral nerves and interfere with recovery of neural function. Because repair of neural injury can be facilitated by inhibiting scar formation, there is a need for a treatment to minimize scar formation in the peripheral nervous system.
Regeneration of nerves in the mammalian CNS is more limited, and in the adult CNS, is almost impossible. Since these cells have been shown to be capable of growing when placed in a different setting, it has been hypothesized that the CNS contains inhibitors of neuronal regeneration. Neuronal growth in the brain may also be retarded by gliosis, a process in which astrocytes form glial scars. Posttraumatic epilepsy, which can arise up to several years after head trauma, is associated with glial cerebromeningeal scars. Since minimizing gliosis can both facilitate neuronal regeneration and decrease the likelihood of posttraumatic epilepsy, there is a need for treatments which inhibit gliosis.
The failure of persons with CNS injuries, particularly spinal cord injuries, to regain neural function is at least partially due to steric interference by gliosis and subsequent scar formation. There is a need for a treatment to facilitate repair of CNS injuries by minimizing gliosis and scarring. The need is particularly great for a treatment that, in addition to facilitating healing of recent neural injuries, could aid in the restoration of neural function in a person with a pre-existing neural injury.